Combining Microscopy Assays of Bacteria-Surface Interactions To Better Evaluate Antimicrobial Polymer Coatings.

Validation of the antimicrobial performance of contact-killing polymer surfaces through the experimental determination of bacterial adhesion or viability, is essential for their targeted development and application. However, there is not yet a consensus on the single most appropriate evaluation method or procedure. Combining and benchmarking previously reported assays could reduce the significant variation and misinterpretation of efficacy data obtained from different methods. In this work, we systematically investigated the response of bacterial cells to antiadhesive and antiseptic polymer coatings by combining (i) bulk solution-based, (ii) thin-film spacer-based, and (iii) direct-contact assays. In addition, we evaluated the studied assays using a five-point scoring framework that highlights key areas for improvement. Our data suggest that combined microscopy assays provide a more comprehensive representation of antimicrobial performance, thereby helping to identify effective types of antibacterial polymer coatings. IMPORTANCE We present and evaluate a combination of methods for validating the efficacy of antimicrobial surfaces. Antimicrobial surfaces/coatings based on contact-killing components can be instrumental to functionalize a wide range of products. However, there is not yet a consensus on the single, most appropriate method to evaluate their performance. By combining three microscopy methods, we were able to discern contact-killing effects at the single-cell level that were not detectable by conventional bulk microbiological analyses. The developed approach is considered advantageous for the future targeted development of robust and sustainable antimicrobial surfaces.

Accuracy of tibial positioning in the frontal plane: a prospective study comparing conventional and innovative techniques in total knee arthroplasty.

BACKGROUND: Coronal alignment of the tibial component determines functional outcome and survival in total knee arthroplasty (TKA). Innovative techniques for tibial instrumentation have been developed to improve accuracy and reduce the rate of outliers. METHODS: In a prospective study, 300 patients were allocated to four different groups using a randomization process (two innovative and two conventional) techniques of tibial instrumentation (conventional: extramedullary, intramedullary; innovative: navigation and patient-specific instrumentation (PSI); n = 75 for each group). The aims were to reconstruct the medial proximal tibial angle (MPTA) to 90° and the mechanical tibio-femoral axis (mTFA) to 0°. Both angles were evaluated and compared between all groups three months after the surgery. Patients who presented with a postoperative mTFA > 3° were classified as outliers. RESULTS: The navigation and intramedullary technique both demonstrated that they were significantly more precise in reconstructing a neutral mTFA and MPTA compared to the other two techniques. The odd's ratio (OR) for producing outliers was highest for the PSI method (PSI OR = 5.5, p < 0.05; extramedullary positioning OR = 3.7, p > 0.05; intramedullary positioning OR = 1.7, p > 0.05; navigation OR = 0.04, p < 0.05). We could only observe significant differences between pre- and postoperative MPTA in the navigation and intramedullary group. The MPTA showed a significant negative correlation with the mTFA in all groups preoperatively and in the extramedullary, intramedullary and PSI postoperatively. CONCLUSION: The navigation and intramedullary instrumentation provided the precise positioning of the tibial component. Outliers were most common within the PSI and extramedullary technique. Optimal alignment is dependent on the technique of tibial instrumentation and tibial component positioning determines the accuracy in TKA since mTFA correlated with MPTA pre- and postoperatively.

Relationships between body temperatures and inflammation indicators under physiological and pathophysiological conditions in pigs exposed to systemic lipopolysaccharide and dietary deoxynivalenol.

We studied the constancy of the relationship between rectal and intraabdominal temperature as well as their linkage to inflammatory markers (leucocyte counts, kynurenine-to-tryptophan ratio (Kyn-Trp ratio), tumour necrosis factor alpha (TNF-α) in healthy and in pigs exposed to lipopolysaccharide (LPS) and/or deoxynivalenol (DON). Barrows (n = 44) were fed 4 weeks either a DON-contaminated (4.59 mg DON/kg feed) or a control (CON) diet and equipped with an intraabdominal temperature logger and a multicatheter system (V.portae hepatis, V.lienalis, Vv.jugulares) facilitating infusion of 0.9% NaCl (CON) or LPS (7.5 µg/kg BW) and simultaneous blood sampling. Body temperatures were measured and blood samples taken every 15 min for leucocyte counts, TNF-α and Kyn-Trp ratio. Combination of diet and infusion created six groups: CON_CONjug .-CONpor. , CON_CONjug. -LPSpor. , CON_LPSjug. -CONpor. , DON_CONjug. -CONpor. , DON_CONjug. -LPSpor. , DON_LPSjug. -CONpor. . The relationship between both temperatures was not uniform for all conditions. Linear regression revealed that an intraabdominal increase per 1°C increase in rectal temperature was ~25% higher in all LPS-infused pigs compared to NaCl-infusion, albeit diet and site of LPS infusion modified the magnitude of this difference. Inflammatory markers were only strongly present under LPS influence and showed a significant relationship with body temperatures. For example, leucocyte counts in clinically inconspicuous animals were only significantly correlated to core temperature in DON-fed pigs, but in all LPS-infused groups, irrespective of diet and temperature method. In conclusion, the gradient between body core and rectal temperature is constant in clinically inconspicuous pigs, but not under various pathophysiological conditions. In the latter, measurement of inflammatory markers seems to be a useful completion.

High prevalence of acetabular retroversion in asymptomatic adults: a 3D CT-based study.

AIMS: This study sought to establish the prevalence of the cross over sign (COS) and posterior wall sign (PWS) in relation to the anterior pelvic plane (APP) in an asymptomatic population through reliable and accurate 3D-CT based assessment. MATERIALS AND METHODS: Data from pelvic CT scans of 100 asymptomatic subjects (200 hips) undertaken for conditions unrelated to disorders of the hip were available for analysis in this study. A previously established 3D analysis method was applied to assess the prevalence of the COS and PWS in relation to the APP. RESULTS: Of the 200 included hips, 24% (48) presented a positive COS and 5.5% (11) presented a positive PWS. A combination of COS and PWS was observed in 1% (two) of all hips (1%). CONCLUSION: The high incidence of acetabular retroversion, determined by the COS, shows that this anatomic configuration may not differ in frequency between asymptomatic individuals and patients with symptomatic femoroacetabular impingement (FAI). Patients presenting with hip pain and evidence of FAI should be subjected to strict diagnostic scrutiny and evaluated in the sum of their clinical and radiological presentation. In our cohort of asymptomatic adults, the COS showed a higher incidence than the PWS or a combined COS/PWS. Cite this article: Bone Joint J 2017;99-B:1584-9.

Cognition in aged rhesus monkeys: effect of DHEA and correlation with steroidogenic gene expression.

Estradiol supplementation has been shown to enhance cognitive performance in old ovariectomized rhesus macaques (Macaca mulatta). To determine if similar benefits could be achieved in perimenopausal animals using alternative hormonal supplements, we administered dehydroepiandrosterone (DHEA) to old ovary-intact female rhesus macaques for ∼2.5 months. Using computerized touch screen memory tasks, including delayed response (DR) and delayed matching-to-sample (DMS), we observed improved performance with time in all of the animals but failed to detect a significant effect of DHEA. On the other hand, gene expression profiling disclosed a significant correlation between cognitive performance and the expression of several steroidogenic and steroid-responsive genes. The DR performance was positively correlated with hippocampal expression of AKR1C3 and STAR and negatively correlated with the expression of SDRD5A1. A positive correlation was also found between DMS performance and prefrontal cortical expression of AKR1C3 and a negative correlation with STAR, as well as a negative correlation with the hippocampal expression of HSD11B1 and NR3C1. Taken together, the results suggest that steroidogenic gene regulation within the brain may help to maintain cognitive function during the perimenopausal transition period, despite a decline in sex-steroid levels in the circulation.

[Periprosthetic infections in patients with rheumatism : A challenge]. / Periprothetische Infektion des rheumatologischen Patienten : Eine Herausforderung.

The increasing number of implantations will lead to more periprosthetic infections. Periprosthetic infections in patients with rheumatism, who are often undergoing immunosuppressive treatment, represent a challenge for the treating physicians. The optimal care and treatment therefore necessitate an interdisciplinary agreement between orthopedic surgeons, specialists for infections and rheumatologists.

[Treatment of periprosthetic infections]. / Therapie der periprothetischen Infektion.

The increasing number of prosthesis implantations and higher life expectancy lead to a growing number of periprosthetic infections (PPI). Optimal therapy necessitates interdisciplinary coordination of surgical and antimicrobial treatment. Challenges in the treatment are the increased occurrence of resistant pathogens, selection of adequate antimicrobial and surgical treatment strategies, inappropriate pretreatment and comorbidities of patients. Current treatment concepts lead to a high success rate in terms of infection eradication, when correctly applied. The individual expectations and underlying conditions of each patient must be considered when determining the therapy concept. The first step is to distinguish between acute and chronic infections. In acute infections the prosthesis can be retained but chronic infections necessitate a complete exchange of the prosthesis. Complicating factors, such as compromising soft tissue and bone conditions, osteomyelitis and infections caused by difficult-to-treat bacteria should, however, always be treated by a complete exchange of the prosthesis, even for acute infections. The antimicrobial treatment must be tailored to the causative agent, the surgical strategy as well as comorbidities and drug intolerances of the patient. It is important to distinguish between biofilm-active eradication therapy with rifampicin for gram-positive pathogens and quinolones for gram-negative organisms and suppression therapy. This article gives a structured presentation of the therapy algorithm.

Spider diversity (Arachnida: Araneae) in Atlantic Forest areas at Pedra Branca State Park, Rio de Janeiro, Brazil.

BACKGROUND: There has never been any published work about the diversity of spiders in the city of Rio de Janeiro using analytical tools to measure diversity. The only available records for spider communities in nearby areas indicate 308 species in the National Park of Tijuca and 159 species in Marapendi Municipal Park. These numbers are based on a rapid survey and on an one-year survey respectively. NEW INFORMATION: This study provides a more thorough understanding of how the spider species are distributed at Pedra Branca State Park. We report a total of 14,626 spider specimens recorded from this park, representing 49 families and 373 species or morphospecies, including at least 73 undescribed species. Also, the distribution range of 45 species was expanded, and species accumulation curves estimate that there is a minimum of 388 (Bootstrap) and a maximum of 468 species (Jackknife2) for the sampled areas. These estimates indicates that the spider diversity may be higher than observed.

Tranexamic acid reduces the blood loss and blood transfusion requirements following peri-acetabular osteotomy.

We have investigated the effect of using tranexamic acid (TXA) during peri-acetabular osteotomy (PAO) on peri-operative blood loss and blood transfusion requirements. In addition we analysed whether the use of TXA was associated with an increased risk of venous thromboembolism (VTE) following this procedure. A consecutive series of 96 PAOs, performed by a single surgeon, were reviewed. A total of 48 patients received TXA and 48 did not. The TXA group received a continuous infusion of TXA at a rate of 10 mg/kg/h. The primary outcome measure was the requirement for blood transfusion. Secondary outcomes included total blood loss, the decrease in the level of haemoglobin in the blood, the length of hospital stay, and the complications of this treatment. The mean rate of transfusion was significantly lower in the TXA group (62.5% vs 12.5%, p < 0.001). The mean blood loss was also significantly reduced in the TXA group (1.9 L (standard deviation (SD) 0.9) vs 1.5 L (SD 0.7), p < 0.01). No post-operative episodes of VTE were identified in either group. The use of TXA reduced the blood loss and the rate of transfusion after PAO significantly, without adverse effects such as an increased rate of VTE.

Are lateral compartment osteophytes a predictor for lateral cartilage damage in varus osteoarthritic knees?: Data from the Osteoarthritis Initiative.

We studied whether the presence of lateral osteophytes on plain radiographs was a predictor for the quality of cartilage in the lateral compartment of patients with varus osteoarthritic of the knee (Kellgren and Lawrence grade 2 to 3). The baseline MRIs of 344 patients from the Osteoarthritis Initiative (OAI) who had varus osteoarthritis (OA) of the knee on hip-knee-ankle radiographs were reviewed. Patients were categorised using the Osteoarthritis Research Society International (OARSI) osteophyte grading system into 174 patients with grade 0 (no osteophytes), 128 grade 1 (mild osteophytes), 28 grade 2 (moderate osteophytes) and 14 grade 3 (severe osteophytes) in the lateral compartment (tibia). All patients had Kellgren and Lawrence grade 2 or 3 arthritis of the medial compartment. The thickness and volume of the lateral cartilage and the percentage of full-thickness cartilage defects in the lateral compartment was analysed. There was no difference in the cartilage thickness or cartilage volume between knees with osteophyte grades 0 to 3. The percentage of full-thickness cartilage defects on the tibial side increased from < 2% for grade 0 and 1 to 10% for grade 3. The lateral compartment cartilage volume and thickness is not influenced by the presence of lateral compartment osteophytes in patients with varus OA of the knee. Large lateral compartment osteophytes (grade 3) increase the likelihood of full-thickness cartilage defects in the lateral compartment.

[Hip replacement in patients with neuromuscular disorders]. / Die Hüftendoprothetik bei neuromuskulären Erkrankungen.

BACKGROUND: Primary total hip replacement in patients with neuromuscular disorders is a challenge for the surgeon and the perioperative team. OBJECTIVES: Special considerations have to be given to implant selection as well as surgical approach and surgical technique. METHODS: The paper presents the current literature on total hip replacements in patients with neuromuscular disorders and the authors' personal experience. RESULTS: Interdisciplinary perioperative management, special knowledge of the anatomic and neuromuscular pathology in patients with neuromuscular disorders, as well as detailed preoperative planning are essential to avoid complications. The choice of the surgical approach should be based on the underlying neuromuscular pathology (spastic vs. paralytic) as well as the need to extend the surgery (soft tissue balancing, femoral shortening osteotomy, acetabular reconstruction). In addition to standard implants special acetabular components might be required for patients with an increased risk of postoperative dislocation, and modular femoral components are indicated for patients with excessive femoral anteversion. CONCLUSIONS: Total hip replacement is a successful treatment option for patients with neuromuscular disorders. While most patients will experience pain relief, functional improvements often depend on the underlying neuromuscular disorder and the preoperative function level. The treatment is complex and requires a specialized team to optimize the outcome of the surgery.

The prioritisation of paediatrics and palliative care in cancer control plans in Africa.

BACKGROUND: Given the burden of childhood cancer and palliative care need in Africa, this paper investigated the paediatric and palliative care elements in cancer control plans. METHODS: We conducted a comparative content analysis of accessible national cancer control plans in Africa, using a health systems perspective attentive to context, development, scope, and monitoring/evaluation. Burden estimates were derived from World Bank, World Health Organisation, and Worldwide Palliative Care Alliance. RESULTS: Eighteen national plans and one Africa-wide plan (10 English, 9 French) were accessible, representing 9 low-, 4 lower-middle-, and 5 upper-middle-income settings. Ten plans discussed cancer control in the context of noncommunicable diseases. Paediatric cancer was mentioned in 7 national plans, representing 5127 children, or 13% of the estimated continental burden for children aged 0-14 years. Palliative care needs were recognised in 11 national plans, representing 157 490 children, or 24% of the estimated Africa-wide burden for children aged 0-14 years; four plans specified paediatric palliative needs. Palliative care was itemised in four budgets. Sample indicators and equity measures were identified, including those highlighting contextual needs for treatment access and completion. CONCLUSIONS: Recognising explicit strategies and funding for paediatric and palliative services may guide prioritised cancer control efforts in resource-limited settings.

Detection and management of drug-resistant tuberculosis in HIV-infected patients in lower-income countries.

SETTING: Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons. OBJECTIVE: To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries. DESIGN: We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs. RESULTS: Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages. CONCLUSIONS: Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.

CUTANEOUS INVOLVEMENT OF HODGKIN LYMPHOMA IN A CHILD--CASE REPORT.

Specific cutaneous involvement in Hodgkin Lymphoma is rare and has not been reported in the younger paediatric age group. We report a case of a ten year old girl who presented with specific cutaneous involvement, confirmed using immunohistochemical stains. Treatment with combination chemotherapy resulted in rapid disappearance of the lesions and contrary to the generally poor prognosis associated with most other such reported cases in adults, she has clinically remained disease free two and a half years post treatment. Obtaining an accurate pathological diagnosis is essential to ensure appropriate treatment even in resource limited settings as illustrated by this case.

[Complications after hip osteotomy]. / Komplikationen nach Beckenosteotomien.

Complex deformities of the acetabulum are one of the most common reasons for secondary pelvic osteoarthritis. One option of treatment is osteotomy of the acetabulum close to the joint. The correction of the spatially reduced roof of the femoral head resulting from pelvic dysplasia can minimize the risk of developing secondary osteoarthritis or reduce the progression of an already existing osteoarthritis. The Ganz periacetabular osteotomy (PAO) and Tönnis triple osteotomy procedures are the predominant methods used to correct hip dysplasia in adolescents. Both are complex procedures which bear specific risks and complications, thus requiring very experienced surgeons.

The role of generic medicines and biosimilars in oncology in low-income countries.

Cancer cases are rising in developing countries which are already grappling with high levels of infectious diseases including human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), tuberculosis (TB) and malaria. The United Nations (UN) including the World Health Organisation (WHO) have called on member states to establish strategies to deal with the increasing burden of non-communicable diseases, including cancer, in developing countries. The complexity of cancer care and management calls for innovative approaches in low resource settings especially since these settings are already grappling with huge challenges in healthcare including lack of funds, weak human resource base and lack of treatment guidelines. Whilst the cost of medications is by no means the only high cost in cancer care, the availability of affordable anti-cancer generic drugs and biologically similar therapeutic agents (biosimilars) will go a long way to reduce overall cost of cancer care. The high cost of anticancer medicines has been cited among the reasons whilst patients default in treatment. Non-proprietary anti-cancer agents--generics and biosimilars--often cost several times lower than their innovator branded counterparts. They can reduce the cost of care significantly and their multi-source origin often provide guarantee in supply. The use of generic and biosimilar products is hinged on the assumption that they are of assured quality and of the same pharmaceutical integrity as their innovator counterparts. The use of these products however is associated with challenges that must be understood and addressed. The quality of all generics and biosimilars should be rigorously controlled and assured. Measures to prevent counterfeit and sub-standard generics and biosimilars should be developed and the cold-chain must be maintained for all biosimilars. In addition to these, the WHO is encouraged to develop a prequalification scheme to assist countries without strong regulatory systems to procure anticancer generics and biosimilars of assured quality.

An unusually large spindle cell sarcoma of the tongue in a male child.

Reports of spindle cell sarcoma in the tongue are very rare, and seldom in the child. We report a five-year-old male patient who presented with a massive lesion on the right side of the tongue. This was surgically excised and histologically diagnosed as a Spindle cell Sarcoma. Results of bone marrow aspiration further revealed that about 16% of his bone marrow was infiltrated with abnormal pleomorphic vacuolated cells with bluish cytoplasm, consistent with rhabdomyosarcoma (RMS) cells. The child was treated with surgery and chemotherapy with good initial response, but then died after one year following a relapse.

Effects of conjugated linoleic acids fed to dairy cows during early gestation on hematological, immunological, and metabolic characteristics of cows and their calves.

The aim of the present experiment was to test the stimulation ability of peripheral blood mononuclear cells (PBMC) expressed as stimulation index (SI) of newborn calves and of their dams fed a control fat supplement (CON, n=6) or 50 and 100g/d of a CLA-containing fat supplement (CLA50, n=5, and CLA100, n=6, respectively) during the preceding lactation period for 182 d after calving. The total intake of cis-9,trans-11 and trans-10,cis-12 CLA by groups CLA50 and CLA100 amounted to 4 and 8 g/d each, respectively. For this purpose, blood was collected immediately after parturition from calves before and after colostrum intake, and from cows after parturition and 21 d later. The SI was related to the fatty acid composition of erythrocyte and milk lipids and to various hematological and clinical-chemical parameters. Retrospective evaluation revealed that depletion time (i.e., the individual period elapsed between the day of terminating the feeding of the experimental diet in the preceding lactation period and the day of calving) ranged from 190 to 262 d, which corresponded to fetal exposure times of 19 to 102 d. The SI from cows increased significantly by 77 and 55%, within 21 d after calving according to the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) and Alamar Blue assays, respectively. However, feeding of 50 g of the CLA product failed to demonstrate this increase in the MTT assay. Moreover, SI was significantly lower for calves whose dams belonged to the CLA50 group, whereas stimulation ability was comparable for the PBMC from calves whose mothers were treated with CON and CLA100. Plasma metabolites (total bilirubin, total cholesterol, glucose, nonesterified fatty acids, 3-ß-hydroxybutyrate, total protein, and albumin) and hematological parameters (hematocrit, white blood cell profile) were not significantly influenced by dietary treatments of the cows in the preceding lactation period. Although the fatty acid pattern of erythrocyte lipids of cows remained uninfluenced, that of calves showed alterations due to the feeding type of their dams. For example, C16:0 increased significantly from 14.4 to 16.9% of total fatty acid methyl esters, whereas cis-9,trans-11 CLA increased slightly from 0.11 to 0.15% at the same time in calves when their mothers were fed the CLA100 instead of the CON diet. Fatty acid profile of colostrum was significantly different from that of milk after 3 wk for most of the detected fatty acids, but was not influenced by diet type. In conclusion, feeding a CLA-containing fat supplement during the preceding lactation and gestation period exerted effects on the stimulation ability of PBMC from cows and calves for the subsequent parturition. However, CLA dose effects were inconsistent and require further investigation.

Hormone supplementation during aging: how much and when?

Circulating levels of dehydroepiandrosterone, a major adrenal steroid, show a marked age-related decrease in both humans and nonhuman primates. Because this decrease has been implicated in age-related cognitive decline, we administered supplementary dehydroepiandrosterone to perimenopausal rhesus macaques (Macaca mulatta) to test for cognitive benefits. Although recognition memory improved, there was no benefit to spatial working memory. To address the limitations of this study we developed a hormone supplementation regimen in aged male macaques that more accurately replicates the 24-hr androgen profiles of young animals. We hypothesize that this more comprehensive physiological hormone replacement paradigm will enhance cognitive function in the elderly.

Presentation of retinoblastoma at a paediatric eye clinic in ghana.

BACKGROUND: Retinobalstoma, the commonest childhood malignant intraocular tumour, is usually diagnosed early with over 90% survival rate in developed countries. In developing countries, the diagnosis is late resulting in less than 50% survival. OBJECTIVE: To determine retinoblastoma stages at presentation and patients' outcomes. DESIGN: Retrospective case series. METHODS: The clinical and histopathological records of children with retinoblastoma seen from May 2004 to December 2005 were studied. Data was analysed for mode of presentation, laterality, clinical staging using Reese-Ellsworth (R-E) classification, histopathological high risk features (HHRF) for metastasis, and patient outcome. SETTING: Ophthalmology Unit, Korle-Bu Teaching Hospital, Ghana. RESULTS: Twenty-three patients presented with retinoblastoma over the period. Males were 12(52.2%). The age range from 1 to 84 months, mean 36.3(±22.15) and median (36 months). Nineteen (82.6%) had unilateral and 4(17.4%) bilateral disease. The common clinical presentations were leukocoria in 20(87.0%), proptosis 8(34.8%), strabismus 5(21.7%) and red eye 5(21.7%). The clinical features were commensurate with R-E stage V in 20(87.0%) patients, 2(8.7%) with orbital recurrence and 1(4.3%) with post-enucleation anophthalmos. HHRFs were present in 9(75%) enucleated eyes with invasion of optic nerve as the commonest site (7/9). The patients were followed up for 1 day to 19 months. Eight abandoned treatment, 2 were discharged for palliative treatment, 2 out of 5 with metastasis died and 6 had no metastases at their last visit. Common sites for metastasis were the bone marrow, brain and orbit. CONCLUSION: Majority of the patients presented with advanced disease manifesting as leukocoria, proptosis, RE stages V disease and poor outcome.